A Phase III Randomized, Placebo-Controlled, Double-Blind Study of Intravenous Calcium/Magnesium to Prevent Oxaliplatin-Induced Sensory Neurotoxicity
- Determine whether calcium gluconate and magnesium sulfate (CaMg) infusions can prevent
or ameliorate chronic, cumulative oxaliplatin-induced neurotoxicity in patients
receiving FOLFOX combination chemotherapy for stage II, III or IV colorectal cancer.
- Determine whether CaMg infusions can increase the cumulative oxaliplatin doses that can
be delivered without chronic neurotoxicity.
- Determine whether CaMg infusions can ameliorate the acute neuropathy associated with
- Determine whether CaMg infusions cause any adverse events.
- Investigate whether CaMg infusions influence quality of life, fatigue, and activities
of daily living of these patients.
- Determine if polymorphisms in the GSTP1 gene predict early onset of oxaliplatin-induced
OUTLINE: This is a randomized, placebo-controlled, double-blind, multicenter study. Patients
are stratified according to age (< 65 vs > 65), gender, and chemotherapy regimen (FOLFOX4 vs
modified FOLFOX6). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes
immediately before and after each oxaliplatin administration (once every 2 weeks) of
their assigned chemotherapy regimen.
- Arm II: Patients receive a placebo IV over 30 minutes immediately before and after each
oxaliplatin administration (once every 2 weeks) of their assigned chemotherapy regimen.
In both arms, treatment continues until chemotherapy is discontinued (approximately 6
Patients complete quality of life questionnaires on day 1, a symptom experience diary on
days 2-5 of their chemotherapy regimen, and questionnaires at 1 and 3 months after
completion of study treatment.
Blood samples are collected at baseline and tested for the GSTP1 gene.
After completion of study treatment, patients are followed for at least 3 months.
PROJECTED ACCRUAL: A total of 300 patients will be accrued for this study.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care
Percentage of Patients With Oxaliplatin-induced Grade 2+ Chronic Neuropathic Adverse Event
Neuropathic adverse events were assessed by Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Neurotoxicity evaluation grade: loss of deep tendon reflexes or paresthesia, including tingling, but not interfering with function (Grade 1); objective sensory alteration or paresthesia, including tingling, interfering with function, but not with activities of daily living (Grade 2); sensory alteration or paresthesia interfering with activities of daily living (Grade 3); permanent sensory losses that are disabling (Grade 4)
Charles L. Loprinzi, MD
United States: Federal Government
|CCOP - Iowa Oncology Research Association||Des Moines, Iowa 50309-1016|
|Sanford Cancer Center at Sanford USD Medical Center||Sioux Falls, South Dakota 57117-5039|
|Medical X-Ray Center, PC||Sioux Falls, South Dakota 57105|
|Avera Cancer Institute||Sioux Falls, South Dakota 57105|
|John Stoddard Cancer Center at Iowa Methodist Medical Center||Des Moines, Iowa 50309|
|MBCCOP - Medical College of Georgia Cancer Center||Augusta, Georgia 30912-3730|
|John Stoddard Cancer Center at Iowa Lutheran Hospital||Des Moines, Iowa 50316-2301|
|Mercy Capitol Hospital||Des Moines, Iowa 50307|
|Medical Oncology and Hematology Associates at John Stoddard Cancer Center||Des Moines, Iowa 50309|
|Medical Oncology and Hematology Associates at Mercy Cancer Center||Des Moines, Iowa 50314|
|Mercy Cancer Center at Mercy Medical Center - Des Moines||Des Moines, Iowa 50314|
|Bismarck Cancer Center||Bismarck, North Dakota 58501|
|Mid Dakota Clinic, PC||Bismarck, North Dakota 58501|
|Medcenter One Hospital Cancer Care Center||Bismarck, North Dakota 58501|